Simon Deycmar’s secondment in Essen, Germany

Simon Deycmar, a RADIATE-ITN Early Stage Researcher (ESR) from University Hospital Zurich, describes his 3 week secondment in Essen, Nov 2018

The aim of my PhD is to elucidate on a cellular level, why proton and photon radiotherapy results in different clinical outcomes and especially, how the DNA double strand break (DSB) repair, subsequent to the respective irradiation, differs. The DNA double strand break repair is mainly accomplished by the fast but erroneous Non-homologous end joining (NHEJ) and additionally, the more laborious, but theoretically error-free, Homologous recombination repair (HRR). Previous data strongly suggests a dependence of proton-induced DSBs on the repair by HRR, which could provide an opportunity for improved patient stratification depending on the genetic background, respectively for combination therapy with HRR-corrupting drugs. Therefore, I combined proton radiotherapy with Ganetespib to inhibit HSP90, a protein that fixes and stabilizes versatile proteins such as HRR key proteins FANCD2, BRCA1, BRCA2, or FANCA and therefore demonstrated a downregulating effect of HRR. [1-3] Recent data, suggests a synergistic effect of Ganetespib and proton irradiation on reduced cancer cell survival. As a next step, we would like to investigate this effect on the direct level of damaged DNA and how the cellular repair can deal with it, upon Ganetespib treatment which can be achieved by alkaline COMET assay.

In order to establish and train in the use of COMET assays, I have visited the laboratory of Prof. Dr. Verena Jendrossek at the Institute of Cell Biology (Tumor Research), located at the campus of the University Hospital Essen (Germany). Versatile research areas such as tumor metabolism or tumor microenvironment and also DNA repair are covered by the group of Prof. Jendrossek. Moreover, the close connection to the West German Proton Therapy Center Essen (WPE) allowed me to combine my drug of interest with proton irradiation when performing this assay.

In addition, to practicing COMET assays and discussing my scientific ideas with people from different scientific backgrounds, I highly appreciated the opportunity to use the irradiation facilities at another proton radiotherapy center and work in another lab. This allowed me to broaden my knowledge, gave me further insight into the versatile irradiation schemes of proton facilities and also a new point of view regarding my research project. This secondment also enabled me to experience another culture and visit famous German sights such as Aachen Cathedral and the grave of Charlemagne. In summary, I achieved a great deal in a short period of time and although hard work, it was an exciting and motivating time and worth the effort. It has boosted my scientific drive for future projects.

  1. Kramer, D., et al., Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells. Cell Death Differ, 2017. 24(2): p. 300-316.
  2. Noguchi, M., et al., Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Biochem Biophys Res Commun, 2006. 351(3): p. 658-63.
  3. Stecklein, S.R., et al., BRCA1 and HSP90 cooperate in homologous and non-homologous DNA double-strand-break repair and G2/M checkpoint activation. Proc Natl Acad Sci U S A, 2012. 109(34): p. 13650-5.